Immunomodulation Therapy + Radiation for Metastatic Breast Cancer

Recruiting at 2 trial locations

Overseen By Kimberly Arieli

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Roswell Park Cancer Institute

Must not be taking: Immunosuppressants, Chemotherapy, Immunotherapy, others

Disqualifiers: Autoimmune disease, HER2+ cancer, Mood disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining immunomodulation therapy, which boosts the immune system, and radiation can safely and effectively treat certain metastatic cancers, such as melanoma, skin cancers, sarcomas, and a specific type of breast cancer. The treatments encourage the immune system to recognize and attack cancer cells. Participants are divided into two treatment groups, one of which includes additional medications administered in various ways to determine the most effective approach. This trial may suit individuals with cancer that cannot be surgically removed, has spread to other parts of the body, and is located in areas like the skin or lymph nodes. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain medications. If you are currently on systemic immunosuppressive agents, you must stop them at least 3 weeks before joining the trial. Additionally, you cannot use targeted therapies or chemotherapy within 2 weeks before starting the trial, but endocrine therapy is allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CDX-1140, one of the treatments in the trial, was well-tolerated in past studies. Among 12 patients with advanced cancer, the treatment did not cause severe side effects that required discontinuation. Some patients even experienced tumor shrinkage.

Poly ICLC has also undergone study, particularly in combination with other treatments. While detailed safety information remains less clear, it has been used in similar situations without major problems reported.

The recombinant Flt3 Ligand, another treatment in this trial, showed promise in earlier studies. Serious side effects requiring discontinuation were rare, occurring in less than 5% of participants, suggesting it is generally safe for most people.

In summary, these treatments have been tested in humans before and are generally well-tolerated. However, as this is a Phase 1 trial, the main goal is to further assess safety, which means there could be risks that are not yet fully understood. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for metastatic breast cancer because they combine immunomodulation with radiation in a novel way. Unlike traditional treatments that primarily focus on chemotherapy or hormone therapy, these investigational therapies use a combination of recombinant Flt3 ligand, CDX-1140, and Poly ICLC to stimulate the immune system directly. Cohort A leverages these immunomodulators with radiation to target cancer cells more precisely, while Cohort B adds pembrolizumab and tocilizumab to potentially enhance immune response further. This innovative approach aims to improve the body's ability to fight cancer and potentially lead to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for metastatic breast cancer?

In this trial, participants in different cohorts will receive various combinations of treatments. Research has shown that CDX-1140, administered to Cohort B alongside pembrolizumab, shows early promise in treating certain solid tumors. Poly-ICLC, included in both Cohort A and Cohort B, acts as a strong immune booster, helping the body recognize and attack cancer cells. Studies have found that recombinant Flt3 ligand, also part of both cohorts, can activate important immune cells, though its direct effect on tumors remains unclear. Together, these treatments aim to enhance the immune system's ability to fight cancer cells more effectively. Initial results appear promising, but further research is needed to confirm their effectiveness. ^{2 5 6 7 8}

Who Is on the Research Team?

Fumito Ito, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced cancers (melanoma, SCC, Merkel cell carcinoma, sarcomas, HER2/neu(-) breast cancer) that can't be removed by surgery. Participants must have measurable disease and agree to receive injections of CDX-301, CDX-1140, poly-ICLC and radiation therapy. They should not have had recent heart issues or other invasive cancers in the last 3 years and must not be pregnant.

Inclusion Criteria

I am willing to have a biopsy of my lesion.

I need radiation therapy for symptom relief or to control the cancer, as advised by my oncologist.

My tumor is in the breast, skin, or lymph nodes, measures 2-7 cm, and can be safely injected.

Exclusion Criteria

Patients with uncontrolled diseases other than cancer may be excluded if after consultation with PI and research team it is decided it might affect the treatment efficacy or toxicity

I'm sorry, it seems like the sentence got cut off. It looks like the criterion is incomplete. Can you please provide the full criterion so that I can help you rewrite it in plain language?

My cancer was caused by previous radiation therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive recombinant Flt3 ligand intratumorally on days 1-5, undergo radiation therapy on day 8 or 9, and receive CDX-1140 and Poly-ICLC intratumorally on day 9 or 10. Treatment repeats every 21 days for 4 cycles.

12 weeks

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 3-6 months for 2 years.

2 years

Follow-up visits every 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• CDX-1140
• Poly ICLC
• Radiation Therapy
• Recombinant Flt3 Ligand

Trial Overview The trial tests a combination of radio-immunotherapy treatments including CDX-301 to boost immune cells called dendritic cells; radiation therapy to kill tumor cells; CDX-1140 and Poly-ICLC to activate the immune system against cancer. It aims to see how well these work together in treating patients with unresectable metastatic solid tumors.

How Is the Trial Designed?

Group I: Cohort B (immunomodulators, radiation therapy) Experimental Treatment 6 Interventions

Patients receive recombinant Flt3 ligand IT on days 1-5 and also receive pembrolizumab (IV), tocilizumab (SC) as well as undergo radiation therapy on day 8 or 9. Patients also receive agonistic anti-CD40 monoclonal antibody IT and IV over 90 minutes and Poly-ICLC IT on day 9 or 10. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Cohort A (immunomodulators, radiation therapy) Experimental Treatment 4 Interventions

Patients receive recombinant Flt3 ligand IT on days 1-5 and undergo radiation therapy on day 8 or 9. Patients also receive agonistic anti-CD40 monoclonal antibody CDX-1140 IT and Poly-ICLC IT on day 9 or 10. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

CXCR4-directed endoradiotherapy using radiolabeled pentixather was administered to 22 patients with heavily pretreated hematopoietic malignancies, showing a favorable safety profile with manageable adverse effects.

While all patients experienced cytopenias, the overall nephro- and hepatotoxicity was low, indicating that this novel treatment approach is well tolerated and can be effectively used before stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side Effects of CXC-Chemokine Receptor 4-Directed Endoradiotherapy with Pentixather Before Hematopoietic Stem Cell Transplantation. Maurer, S., Herhaus, P., Lippenmeyer, R., et al.[2020]

Radiotherapy not only kills cancer cells by damaging their DNA but also enhances the immune response against tumors through mechanisms like bystander effects and the normalization of tumor blood vessels.

Recent studies suggest that combining radiotherapy with immunotherapy can improve treatment outcomes, as radiotherapy may boost the effectiveness of immune-based treatments, making it a promising strategy in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial Watch: Anticancer radioimmunotherapy. Vacchelli, E., Vitale, I., Tartour, E., et al.[2021]

Immune checkpoint inhibitors (ICIs) have expanded the range of cancers that can be treated with immunotherapy, but not all patients or cancer types respond effectively, highlighting the need for personalized treatment approaches.

Combining ICIs with radiation therapy (RT) shows promise due to RT's immunomodulatory effects, but further research is needed to optimize treatment schedules, manage side effects, and identify biomarkers for predicting patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A perspective on the impact of radiation therapy on the immune rheostat. McBride, WH., Ganapathy, E., Lee, MH., et al.[2018]

The study demonstrated that combining pulsed radiation therapy (12Gyx2) with the anti-CTLA-4 immune checkpoint inhibitor significantly improved survival and delayed tumor growth in a mouse model of non-small cell lung adenocarcinoma, indicating enhanced antitumor efficacy.

Pulsed radiation therapy led to an increase in CD4+ effector memory T cells compared to single-cycle radiation, suggesting that this approach may effectively build immune memory and enhance the overall immune response against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed radiotherapy to mitigate high tumor burden and generate immune memory. Sezen, D., Barsoumian, HB., He, K., et al.[2022]

The combination of NBTXR3, high-dose radiation, low-dose radiation, and immune checkpoint inhibitors significantly improved survival rates in a mouse model of anti-PD1-resistant metastatic lung cancer, increasing survival from 0% to 50%.

This treatment enhanced the immune response by increasing CD8 T-cell infiltration and reducing regulatory T cells in the tumors, suggesting that NBTXR3 may help overcome resistance to anti-PD1 therapy by promoting a stronger antitumor immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model. Hu, Y., Paris, S., Barsoumian, H., et al.[2022]

Radiation therapy not only directly kills tumor cells but also modifies the tumor microenvironment, enhancing both local and systemic immune responses against cancer.

Combining radiation therapy with immunotherapy can lead to stronger anti-tumor effects than using either treatment alone, suggesting a promising strategy for improving cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy and radiation. Hiniker, SM., Knox, SJ.[2014]

Combining the CXCR4 inhibitor Plerixafor with standard radio-chemotherapy (RTCT) significantly improved tumor growth delay and reduced lymph node metastases in cervical cancer models, indicating enhanced treatment efficacy.

The addition of Plerixafor did not increase acute intestinal toxicity or cause changes in normal organ morphology, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plerixafor Improves Primary Tumor Response and Reduces Metastases in Cervical Cancer Treated with Radio-Chemotherapy. Chaudary, N., Pintilie, M., Jelveh, S., et al.[2021]

In a study using a murine lung cancer model, the combination of anti-OX40 monoclonal antibody and radiotherapy significantly prolonged survival and was more effective than either treatment alone, indicating a promising therapeutic strategy for lung cancer.

The effectiveness of this combination therapy was found to be primarily dependent on CD8(+) T-cells, which were enhanced in the lymph nodes of irradiated mice, suggesting that this approach not only targets tumors but also boosts the immune response against cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-OX40 monoclonal antibody therapy in combination with radiotherapy results in therapeutic antitumor immunity to murine lung cancer. Yokouchi, H., Yamazaki, K., Chamoto, K., et al.[2022]

The combination of NBTXR3 nanoparticles with immunoradiotherapy (anti-PD1 and anti-CTLA4) significantly enhanced antitumor immune responses and reduced immune suppression in a mouse model of metastatic lung cancer, leading to the eradication of both primary and secondary tumors.

This treatment approach resulted in a 75% survival rate among the mice, with survivors showing a long-lasting antitumor memory immune response, suggesting potential for effective clinical applications in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NBTXR3 improves the efficacy of immunoradiotherapy combining nonfucosylated anti-CTLA4 in an anti-PD1 resistant lung cancer model. Hu, Y., Paris, S., Bertolet, G., et al.[2022]

CDX-301 has shown significant efficacy as a medical countermeasure against irradiation-induced lethality in mice, providing protection when administered both before and after exposure to gamma radiation.

The treatment accelerated recovery from blood cell loss and bone marrow damage, while also enhancing T cell profiles, indicating its potential for use in managing acute radiation syndrome in real-world radiological emergencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDX-301: a novel medical countermeasure for hematopoietic acute radiation syndrome in mice. Satyamitra, M., Cary, L., Dunn, D., et al.[2021]

Poly ICLC acts as an interferon inducer and has multiple therapeutic properties, including antiviral, antitumor, and immunoregulatory effects.

In studies with mice and rabbits, administering poly ICLC led to the production of anti-IC antibodies in their serum, suggesting an immune response that could be beneficial for therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poly ICLC induces anti-IC antibodies in mice and rabbits. Granados, EN., Alm, T., O'Malley, JA., et al.[2020]

Stereotactic ablative body radiotherapy (SABR) not only delivers high doses of radiation to tumors but also has significant immunomodulatory effects that can enhance the body's anti-tumor immune response.

Combining SABR with immune checkpoint inhibitors can improve treatment outcomes by overcoming tumor-induced immunosuppression and preparing tumors for a stronger adaptive immune response, as shown in early phase clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The optimism surrounding stereotactic body radiation therapy and immunomodulation. Tharmalingam, H., Hoskin, PJ.[2018]

Combining radiotherapy with immunological pharmaceuticals like checkpoint inhibitors may enhance the abscopal response, where untreated tumors shrink after treatment, making this phenomenon more common than before.

Radiotherapy can modify the tumor environment by increasing neoantigen and PD-L1 expression, which may improve the effectiveness of immunotherapies, suggesting that new radiation techniques could work well with recently approved immune-modulating agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of radiation-induced abscopal response: beyond conventional radiotherapy approaches. Tubin, S., Yan, W., Mourad, WF., et al.[2021]

Radioimmunotherapy (RIT) offers a promising treatment for hepatocellular carcinoma (HCC) by using targeted radiation delivered through monoclonal antibodies, potentially providing higher doses to cancer cells while minimizing damage to healthy tissues.

Combining RIT with immune-checkpoint inhibitors (ICIs) and other immunotherapy approaches may enhance treatment outcomes for HCC, as recent advancements suggest that targeting specific antigens on HCC cells could improve the effectiveness of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel antigens for targeted radioimmunotherapy in hepatocellular carcinoma. Pourhamzeh, M., Asadian, S., Mirzaei, H., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS1126

Phase 1 pilot study with dose expansion of chemotherapy ... This is a single arm phase I pilot study of liposomal-doxorubicin, CDX-1140 (CD40 agonist), and CDX-301 (Flt3 ligand) combination therapy in patients with ...

2. onclive.com onclive.com/view/cdx-1140-plus-pembrolizumab-elicits-responses-in-pd-1-pd-l1-resistant-solid-tumors

CDX-1140 Plus Pembrolizumab Elicits Responses in PD-1/ ... The utilization of the anti-CD40 agonist, CDX-1140, in combination with pembrolizumab was generally well tolerated and demonstrated preliminary efficacy.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04616248

NCT04616248 | In Situ Immunomodulation With CDX-301, ... This phase I trial evaluates the safety and effectiveness of in situ immunomodulation with CDX-301, radiotherapy, CDX-1140 and Poly-ICLC (Cohort A) and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05029999

Study Details | NCT05029999 | CD40 Agonist, Flt3 Ligand ... This research study is being done to find out if the immunotherapy drugs called CDX-301 and CDX-1140 in combination with the standard chemotherapy treatment ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8000216/

Agonistic CD40 Antibodies in Cancer Treatment - PMC CD40 agonism combined with gemcitabine/nab-paclitaxel reduced tumor growth more effectively than either modality alone. Regulatory T cells in ...

6. acir.org acir.org/weekly-digests/2025/august/agonist-anti-cd40-shows-promise-in-a-phase-1-clinical-trial

Agonist anti-CD40 shows promise in a phase 1 clinical trial Out of the 12 patients treated with 2141-V11, 11 were evaluable for antitumor activity. A decrease in tumor burden was observed in 6 patients, ...

7. cell.com cell.com/cancer-cell/fulltext/S1535-6108(25)00319-8

Fc-optimized CD40 agonistic antibody elicits tertiary ... Among 12 metastatic cancer patients, 2141-V11 was well tolerated without dose-limiting toxicities. Six patients experienced tumor reduction, including two ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11177954/

Intratumoral Fc-optimized agonistic CD40 antibody induces ... In ten evaluable patients with metastatic cancer, the overall response rate was 20%, with complete responses in two patients (melanoma and breast carcinoma) and ...